Cells represent the primary building blocks of higher biological systems, such as tissues, organs, as well as entire multicellular organisms. In higher organisms, e.g., mammals, cells often interact with one another for such important biological functions as transmitting signals and building macrostructures, including tissues. Cell interaction may also profoundly influence various disease states, such as infectious, immune and autoimmune disorders, primary site or metastatic cancers, thus it is often of great importance to study any specific biological problem in its in vivo context, or at least in a system that somewhat mimics or approximates its in vivo context.
However, due to many technical and theoretical difficulties, doing so is not always possible or practical. For example, in the field of new drug development, traditional studies tend to focus on the effect of a candidate compound on a specific cell type of interest, in isolation from the general biological context in which the cell functions. In other words, this type of study, for various reasons, intentionally or accidentally omits the microenvironment in which the cell operates, and thus it may not come as a surprise when one identifies a promising drug candidate in the initial in vitro study, only to find in later stage drug development that the candidate drug fails in clinical trial.
One case on point is drug development for cancer treatment. Historically, the early stages of anti-cancer drug development have involved high-throughput screening of large libraries of compounds for potential in vitro activity against tumor cell lines. In these screening modalities, tumor cells are studied in conventional in vitro systems, where tumor cells are cultured in isolation from any other cell types with which they might interact in the in vivo local microenvironment of the tumor. These conventional screening strategies have included, e.g., the NCI60 panel of 60 tumor cell lines, which has been the basis for the anti-cancer screening program of the Developmental Therapeutics Program of the National Cancer Institute (NCI). Overall, the NCI60 panel and other similar screening programs in both academia and industry have been useful in identifying candidate anti-cancer compounds, many (but not all) of which have translated in clinical applications for systemic chemotherapy of human malignancies.
Unfortunately, systemic chemotherapy using anti-cancer compounds for human neoplasia, which may have been identified using such methods, is generally not curative. In fact, a key challenge identified in the oncology field for several years now is the contrast between the remarkable in vitro anti-tumor activity exhibited in the past by many conventional and investigational anti-cancer agents, and their typically less impressive clinical activity of these agents when they were eventually tested in clinical trials.
This kind of problem is by no means a unique phenomenon of cancer drug development. Most (if not all) drugs do not affect a single cell type; instead, they act on many different types of living cells in an entire organism. Thus, the ultimate efficacy of a drug not only depends on its effect on its target cell, but also the influence of the microenvironment on the target cell. Thus arguably, all drug development faces the same issue, maybe to different extents. This problem is particularly acute in modern day drug development, where years (if not decades) of research and tremendous amount of human and financial resources are typically devoted to the process.